Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01889 (ankylosing spondylitis)
 5,717 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Despite intensive research during the last three decades, it is still not clear which precise mechanisms determine the interactions between host factors (HLA-B27 and other genes, cytokines, T lymphocytes) and microbial factors leading to the manifestation and chronicity of ankylosing spondylitis (AS). Rheumatologists and histopathologists have focused their interest on decoding the immune-mediated inflammatory processes and on studying new bone formation and ankylosis. Concerning the genetic basis of AS, there is considerable effort in large genome-wide and candidate gene analyses to discover new genes that are associated with AS. Moreover, such genetic studies could identify genomic regions that determine clinical manifestations and the course of disease.
 ...
PMID:[Pathogenesis of ankylosing spondylitis-mechanisms of disease manifestation and chronicity]. 1522 21

Recent success in the treatment of patients with the more severe forms of spondyloarthritides (SpA) has dramatically changed old paradigms. There is evidence that anti-tumor necrosis factor (TNF)-alpha therapy is highly effective in SpA, especially in ankylosing spondylitis (AS) and psoriatic arthritis. Based on recent data on more than 1000 patients with AS and psoriatic arthritis, this treatment seems to be even more effective than in rheumatoid arthritis (RA). The currently available anti-TNFalpha agents, infliximab, etanercept, and adalimumab, are approved for the treatment of RA in the US and in Europe. TNFalpha blockers may even be considered as a first-line treatment in patients with active AS whose condition is not sufficiently controlled with NSAIDs, as in the case of axial disease. There is preliminary evidence that both agents also work in other SpA, such as undifferentiated SpA. There is hope that ankylosis may be preventable, but it remains to be shown whether patients benefit from long-term anti-TNFalpha therapy and whether radiologic progression and ankylosis can be stopped. Furthermore, it seems that anti-TNFalpha therapy can also improve clinical manifestations of other inflammatory spinal disorders, such as sciatica and back pain caused by disc herniation, or possibly even intermittent inflammatory states of degenerative disc disease. Severe adverse events from treatment with anti-TNFalpha continue to be rare. Tuberculosis can be largely prevented by appropriate screening. As it stands now, the benefits of anti-TNFalpha therapy in AS seem to outweigh the shortcomings.
 ...
PMID:Current concepts in the therapy of the spondyloarthritides. 1537 73

The axial skeleton is a target for both spondyloarthritis and rheumatoid arthritis. While conventional radiography allows the clear documentation of the late stages of inflammatory changes, magnetic resonance imaging (MRI) is sensitive enough to depict early inflammatory lesions. It is, therefore, of particular importance for radiologists and clinicians to know the MRI appearances of inflammatory changes of the axial skeleton in rheumatoid diseases. Typical lesions in ankylosing spondylitis and related conditions comprise spondylitis (Romanus lesion), spondylodiscitis (Andersson lesion), arthritis of the apophyseal joints, the costovertebral and costotransverse joints, and insufficiency fractures of the ankylosed vertebral spine (non-inflammatory type of Andersson lesion). Sacroiliitis is associated with chronic changes such as sclerosis, erosions, transarticular bone bridges, periarticular accumulation of fatty tissue and ankylosis. In addition, acute findings include capsulitis, juxta-articular osteitis and the enhancement of the joint space after contrast medium administration. Another important sign of spondyloarthritis is enthesitis, which affects the interspinal and supraspinal ligaments of the vertebral spine and the interosseous ligaments in the retroarticular space of the sacroiliac joints. The main site of manifestation of spinal involvement in rheumatoid arthritis is the cervical spine. Typical changes are the destruction of the atlantoaxial complex by pannus tissue with subsequent atlantoaxial subluxation, basilar impression and erosion of the dens axis. Changes in the lower segments of the cervical spine are destruction of the apophyseal joints resulting in the so-called stepladder phenomenon. Because of the uniform response of the discovertebral complex to different noxae, a number of different conditions must be distinguished on the basis of the patient's clinical findings and history in combination with their imaging appearance. These conditions comprise degenerative disc disease, septic spondylodiscitis, Scheuermann's disease, Paget's disease and diffuse idiopathic skeletal hyperostosis (DISH).
 ...
PMID:Magnetic resonance imaging of the axial skeleton in rheumatoid disease. 1550 Nov 88

Up to 2 in 1,000 adults in the UK have ankylosing spondylitis. This chronic inflammatory disease causes pain and stiffness in the spine and sacroiliac and peripheral joints, and may also affect the eyes, heart and ungs. Characteristic features include ankylosis of the spine with a progressive loss of spinal mobility. Treatment with NSAIDs and physical therapy can provide symptomatic relief of pain and stiffness, but does not modify the course of the disease (e.g. slow or prevent ankylosis). In general, disease-modifying antirheumatic drugs (DMARDs), such as gold, methotrexate and sulfasalazine, have little or no effect in ankylosing spondylitis. [symbol: see text]Etanercept (Enbrel--Wyeth) and [symbol: see text]infliximab (Remicade--Schering-Plough), two drugs which block the inflammatory effect of tumour necrosis factor (TNF), are now licensed for the treatment of patients with severe ankylosing spondylitis whose symptoms have not responded adequately to conventional therapy. Here we review the place of these TNF antagonists in the management of such individuals.
 ...
PMID:TNF antagonists for ankylosing spondylitis. 1576 84

The ank (progressive ankylosis) mutant mouse, which has a nonsense mutation in exon 12 of the inorganic pyrophosphate regulator gene (ank), exhibits aberrant joint ankylosis similar to human ankylosing spondylitis (AS). We previously performed family-based association analyses of 124 Caucasian AS families and showed that novel genetic markers in the 5' flanking region of ANKH (the human homolog of the murine ank gene) are modestly associated with AS. The objective of the present study was to conduct a more extensive evaluation of ANKH variants that are significantly associated with AS and to determine whether the association is gender specific. We genotyped 201 multiplex AS families with nine ANKH intragenetic and two flanking microsatellite markers, and performed family-based association analyses. We showed that ANKH variants located in two different regions of the ANKH gene were associated with AS. Results of haplotype analyses indicated that, after Bonferroni correction, the haplotype combination of rs26307 [C] and rs27356 [C] is significantly associated with AS in men (recessive/dominant model; P = 0.004), and the haplotype combination of rs28006 [C] and rs25957 [C] is significantly associated with AS in women (recessive/dominant model; P = 0.004). A test of interaction identified rs26307 (i.e. the region that was associated in men with AS) as showing a difference in the strength of the association by gender. The region associated with AS in women only showed significance in the test of interaction among the subset of families with affected individuals of both genders. These findings support the concept that ANKH plays a role in genetic susceptibility to AS and reveals a gender-genotype specificity in this interaction.
 ...
PMID:ANKH variants associated with ankylosing spondylitis: gender differences. 1589 38

Blocking tumor necrosis factor-alpha either with monoclonal antibodies or with soluble receptor constructs has been proven to be effective with an acceptable safety profile in patients with rheumatoid arthritis, and more recently also in the diseases belonging to the spondyloarthropathy concept. Nevertheless multiple questions still remain unresolved especially concerning longer-term treatment. Data from a recent manuscript by Baraliakos and colleagues seem to indicate that at least for the vast majority of ankylosing spondylitis patients treatment with infliximab can not be withdrawn, if one wants to control disease activity in a continuous way. Although still unproven, this might be of crucial importance with regard to structure modification and prevention of ankylosis in this chronic inflammatory disorder.
 ...
PMID:Tumor necrosis factor-alpha blockade in ankylosing spondylitis: a potent but expensive anti-inflammatory treatment or true disease modification? 1589 30

Pleuropulmonary involvement was long described as an uncommon and late event in the course of ankylosing spondylitis (AS). This belief was based on studies that relied on symptoms and chest radiographs to evaluate the lungs. However, pleuropulmonary involvement in AS patients is usually asymptomatic, and the early lesions are undetectable on chest radiographs. Apical fibrosis, interstitial infiltrates, and pleural thickening were considered to be the main patterns. However, the introduction of high-resolution computed tomography (HRCT) has led to the description of many pulmonary abnormalities that are clinically silent and undetectable on plain radiographs. These abnormalities mainly affect the interstitium and have no influence on respiratory function, which is dependent on the severity of chest wall inflammation or ankylosis in recent-onset and established AS, respectively. Cytological and histological studies suggest that, in common with uveitis and aortic regurgitation, the structural lung changes shown by HRCT may be specific of AS.
 ...
PMID:Pleuropulmonary involvement in ankylosing spondylitis. 1637 3

We describe a case of difficult intubation in a patient suffering from ankylosing spondylitis undergoing total hip replacement surgery. The anesthetic management of 42 year old patient with difficult airway is discussed. Failure of epidural anesthesia procedure necessitated general anesthesia. The problems of performing awake fibreoptic intubation and other alternative techniques to secure the airway are described. Cervical spine involvement in ankylosing spondylitis is of great concern for the anesthetist. Longstanding progressive course of this disease leads to fibrosis, ossification and ankylosis of entire spine and sacroiliac joints. Cervical spine mobility is decreased and in severe cases total fixity occurs in a flexed position. Patient may also have atlanto-occipital and temporo-mandibular joint involvement as well. Cricoarytenoid cartilages involvement may result in upper airway compromise. Furthermore cervical spine vertebrae are prone to fractures, especially on hyperextension and may lead to spinal cord transection and quadriplegia. In this case report we describe the airway management of such patient with fixed rigidity of cervical spine and thoracolumbar kyphosis.
 ...
PMID:Management of difficult intubation in a patient with ankylosing spondylitis--a case report. 1643 12

Conventional radiography is still the standard method of imaging in PsA since it displays many joints at the same time, thereby allowing different types of joint involvement to be recognized. Moreover, thanks to the high resolution of radiography, bony changes in a single joint are depicted in a brilliant way. Several features of psoriatic arthritis allow the distinction from rheumatoid arthritis, including the frequent involvement of the distal interphalangeal joints, asymmetry of joint involvement, axial involvement of finger joints, oligoarticular involvement; however, symmetric polyarthritis is also possible. At the level of the single joint, there are signs of severe destructive changes potentially leading to mutilation and at the same time signs of periostal bone proliferation and ankylosis may be present. Bony proliferation and/or osteolysis are not restricted to the joint region but can affect also the total phalanx with bone apposition or concentric osteolysis which may lead to a complete disappearance of phalanxes. For purposes of quantification of radiographic changes scoring methods are used that were originally developed for rheumatoid arthritis. So far, there is only one validated scoring method that was specifically designed for PsA and that takes into account both features of PsA, damage as well as proliferation of bone. In contrast to conventional radiography, MRI and sonography are able to visualize inflammatory processes within the soft tissue (joint capsules, tendon sheaths, tendon insertions, etc.), allowing an estimation of disease activity. Scintigraphy is nonspecific and can only be used to detect clinically silent inflammatory spots. The relatively frequent spinal (axial) involvement is similar to that seen in ankylosing spondylitis. However, unilateral sacroiliitis, asymmetry of syndesmophytes and development of parsyndesmophytes may distinguish PsA from ankylosing spondylitis. While conventional radiography demonstrates the bony consequences of inflammation in the spine, MRI also shows the active inflammatory changes in sacroiliacal joints and vertebrae.
 ...
PMID:[Imaging methods in rheumatology: imaging in psoriasis arthritis (PsA)]. 1645 Jan 48

Ankylosing spondylitis is a chronic, inflammatory rheumatic disease which etiology and pathogenesis are not yet fully understood. The inflammation involves the spine and also the peripheral joints might be affected in some cases resulting in a progressive ankylosis, restricted mobility, significant disability, loss of productivity and decreased quality of life. Gene technology based new drugs of the past decade, the biologic agents, offer an alternative opportunity for the treatment of ankylosing spondylitis in comparison with the previous drugs with doubtful efficiency. In Hungary infliximab and etanercept has been registered for ankylosing spondylitis. The aim of this study was to evaluate the efficacy of infliximab and etanercept by the available randomised controlled trials. A systematic search of the literature was performed from 01. 01. 2000 to 08. 31. 2005. and the relevant publications were analysed following the concepts of evidence based medicine. 7 double blind, randomised, placebo controlled trials were identified, three for infliximab (n = 389) and four for etanercept (n = 431). Although the inclusion criteria, the duration of the trials and the primary endpoints were different, the results confirm that both drugs significantly decrease symptoms and disease activity, and this effect is sustained during the therapy, nevertheless half of the patients did not achieve the standardised criteria of 50% decrease in disease activity. Both agents are well tolerated by patients. The outcomes of long-term therapy are reassuring by open extension studies of three years. Guidelines for biologic therapy has been developed in Hungary determining the target patient group, the conditions of the therapy and also an arthritis centre network has been established. Though individual admission is feasible, biologic drugs are not under reimbursement in Hungary. High drug costs makes the implementation of this new therapeutic opportunity difficult in the daily medical practice.
 ...
PMID:[The role of biologic agents in the therapy of ankylosing spondylitis]. 1689 82


<< Previous 1 2 3 4 5 6 7 8 9 10